| Effective Gene Delivery Using Stimulus-Responsive Catiomer Designed with Redox-Sensitive Disulfide and Acid-Labile Imine Linkers. | |
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MedLine Citation:
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PMID: 22443494 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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A dual stimulus-responsive mPEG-SS-PLL(15)-glutaraldehyde star (mPEG-SS-PLL(15)-star) catiomer is developed and biologically evaluated. The catiomer system combines redox-sensitive removal of an external PEG shell with acid-induced escape from the endosomal compartment. The design rationale for PEG shell removal is to augment intracellular uptake of mPEG-SS-PLL(15)-star/DNA complexes in the presence of tumor-relevant glutathione (GSH) concentration, while the acid-induced dissociation is to accelerate the release of genetic payload following successful internalization into targeted cells. Size alterations of complexes in the presence of 10 mM GSH suggest stimulus-induced shedding of external PEG layers under redox conditions that intracellularly present in the tumor microenvironment. Dynamic laser light scattering experiments under endosomal pH conditions show rapid destabilization of mPEG-SS-PLL(15)-star/DNA complexes that is followed by facilitating efficient release of encapsulated DNA, as demonstrated by agarose gel electrophoresis. Biological efficacy assessment using pEGFP-C1 plasmid DNA encoding green fluorescence protein and pGL-3 plasmid DNA encoding luciferase as reporter genes indicate comparable transfection efficiency of 293T cells of the catiomer with a conventional polyethyleneimine (bPEI-25k)-based gene delivery system. These experimental results show that mPEG-SS-PLL(15)-star represents a promising design for future nonviral gene delivery applications with high DNA binding ability, low cytotoxicity, and high transfection efficiency. |
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Authors:
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Xiaojun Cai; Chunyan Dong; Haiqing Dong; Gangmin Wang; Giovanni M Pauletti; Xiaojing Pan; Huiyun Wen; Isaac Mehl; Yongyong Li; Donglu Shi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-26 |
Journal Detail:
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Title: Biomacromolecules Volume: - ISSN: 1526-4602 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100892849 Medline TA: Biomacromolecules Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Institute for Advanced Materials and Nano Biomedicine, School of Medicine, ‡Department of Oncology, Shanghai East Hospital, and §School of Life Science and Technology, Tongji University , Shanghai 200092, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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